The eIF2α kinase PERK limits the expression of hippocampal metabotropic glutamate receptor-dependent long-term depression

Mimi A. Trinh, Tao Ma, Hanoch Kaphzan, Aditi Bhattacharya, Marcia D. Antion, Douglas R. Cavener, Charles A. Hoeffer, Eric Klann

Research output: Contribution to journalArticlepeer-review


The proper regulation of translation is required for the expression of long-lasting synaptic plasticity. A major site of translational control involves the phosphorylation of eukaryotic initiation factor 2 α (eIF2α) by PKR-like endoplasmic reticulum (ER) kinase (PERK). To determine the role of PERK in hippocampal synaptic plasticity, we used the Cre-lox expression system to selectively disrupt PERK expression in the adult mouse forebrain. Here, we demonstrate that in hippocampal area CA1, metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) is associated with increased eIF2α phosphorylation, whereas stimulation of early- and late-phase long-term potentiation (E-LTP and L-LTP, respectively) is associated with decreased eIF2α phosphorylation. Interesting, although PERK-deficient mice exhibit exaggerated mGluR-LTD, both E-LTP and L-LTP remained intact. We also found that mGluR-LTD is associated with a PERK-dependent increase in eIF2α phosphorylation. Our findings are consistent with the notion that eIF2α phosphorylation is a key site for the bidirectional control of persistent forms of synaptic LTP and LTD and suggest a distinct role for PERK in mGluR-LTD.

Original languageEnglish
Pages (from-to)298-304
Number of pages7
JournalLearning and Memory
Issue number5
StatePublished - May 2014


  • Analysis of Variance
  • Animals
  • Biophysical Phenomena / drug effects
  • Biophysical Phenomena / genetics
  • CA1 Region, Hippocampal / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • DNA-Binding Proteins / metabolism
  • Electric Stimulation
  • In Vitro Techniques
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Methoxyhydroxyphenylglycol / analogs & derivatives
  • Methoxyhydroxyphenylglycol / pharmacology
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Receptors, Metabotropic Glutamate / metabolism*
  • Transcription Factors / metabolism
  • eIF-2 Kinase / genetics
  • eIF-2 Kinase / metabolism*

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


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